Blog

• MINDACT:
  • Was the first large prospective randomized trial to test whether the 70-gene signature (MammaPrint):
    • Could help spare adjuvant chemotherapy in patients with early breast cancer:
      • Especially when clinical risk and genomic risk disagreed
  • Its key contribution was showing that some patients who appear high-risk by traditional clinicopathologic criteria:
    • Still have an excellent outcome without chemotherapy if they are genomically low-risk
• Trial design:
  • MINDACT enrolled 6,693 women with early-stage breast cancer
  • Patients were assigned both a clinical risk estimate and a genomic risk estimate:
    • Clinical risk was based on:
      • A modified Adjuvant! Online tool
    • Genomic risk was based on:
      • The 70-gene signature
  • Patients with concordant low risk generally avoided chemotherapy
  • Those with concordant high risk received it
  • Those with discordant risk:
    • Were randomized to treatment decisions based on either the clinical or genomic result:
      • The primary test population was the clinical high-risk / genomic low-risk group 
• Primary finding:
  • In patients with high clinical risk but low genomic risk:
    • Who did not receive chemotherapy:
      • The 5-year distant metastasis-free survival (DMFS) was 94.7% (95% CI 92.5–96.2):
        • Which met the study’s predefined benchmark for safety
      • This was the practice-changing result:
        • It supported omission of chemotherapy in selected patients despite unfavorable conventional features
• Longer-term follow-up:
  • With longer follow-up, the benefit of chemotherapy in the clinical high-risk / genomic low-risk group remained small overall
  • The 2021 update reported that the 8-year DMFS for this group was 92.0% with chemotherapy vs 89.4% without chemotherapy, an absolute difference of 2.6 percentage points
    • The authors concluded that the 70-gene signature continues to identify a group with excellent outcomes and only a limited average chemotherapy benefit
• Age-related nuance:
  • The most important nuance for multidisciplinary decision-making is age
  • In the updated analysis, the apparent chemotherapy benefit was not seen in women older than 50 years, while a potentially clinically relevant benefit appeared in women 50 years or younger
    • This raises the same question seen in other adjuvant trials:
      • How much of the effect reflects true cytotoxic benefit versus ovarian suppression / menopausal effect in younger patients
        • For the surgeon, this means a low-genomic-risk result should still be interpreted in the context of menopausal status and age
• Node-positive relevance:
  • A major practical strength of MINDACT is that it included not only node-negative disease but also patients with 1 to 3 positive nodes:
    • Making it more broadly relevant than node-negative-only genomic trials
  • For surgical oncologists, this is especially useful after lumpectomy or mastectomy when pathology shows limited nodal disease and the team is deciding whether anatomy alone should drive chemotherapy recommendations
• Ultralow-risk subgroup:
  • A later MINDACT analysis identified an ultralow-risk subgroup by the 70-gene assay
  • These patients had exceptionally favorable outcomes:
    • Including an 8-year distant metastasis-free interval of 97.0% and 8-year breast cancer-specific survival above 99%
  • This supports even more confidence in de-escalation discussions in carefully selected patients with highly favorable biology
• What this means for the surgical oncologist:
  • MINDACT matters because it reinforces that postoperative planning in early breast cancer is no longer based on tumor size, grade, and nodal status alone:
    • A patient with a large tumor or limited nodal involvement may still have a genomically low-risk cancer with only modest absolute chemotherapy benefit
  • In practical terms:
    • A surgeon should think about which ER-positive / HER2-negative patients may benefit from genomic testing as part of adjuvant planning
    • A clinical high-risk / genomic low-risk result can support a discussion about omitting chemotherapy, particularly in older than 50 patients
    • In younger / premenopausal patients, especially with higher tumor burden or limited node-positive disease:
      • The discussion remains more nuanced and should be individualized
• Bottom line:
  • MINDACT showed that biology can meaningfully refine risk beyond standard pathology
  • For the surgical oncologist, the main takeaway is that a patient who looks high-risk on anatomic grounds may still have a sufficiently favorable genomic profile to justify avoiding adjuvant chemotherapy:
    • Particularly if she is older than 50 years and has ER-positive / HER2-negative early breast cancer
• Key references:
  • Cardoso F, van’t Veer LJ, Bogaerts J, et al. 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. N Engl J Med. 2016;375:717-729. 
  • Piccart M, van’t Veer LJ, Poncet C, et al. 70-gene signature as an aid for treatment decisions in early breast cancer: updated results of the phase 3 randomised MINDACT trial with an exploratory analysis by age. Lancet Oncol. 2021;22:476-488. 
  • Lopes Cardozo JMN, Drukker CA, Rutgers EJT, et al. Outcome of Patients With an Ultralow-Risk 70-Gene Signature in the MINDACT Trial. J Clin Oncol. 2022;40:1335-1345.

• TAILORx (Trial Assigning Individualized Options for Treatment):
  • Was the landmark prospective trial that validated use of the 21-gene recurrence score (Oncotype DX):
    • To guide adjuvant chemotherapy decisions in women with:
      • HR-positive, HER2-negative, axillary node-negative early breast cancer
  • Its main practice-changing contribution was showing that:
    • Most women with an intermediate recurrence score:
      • Do not benefit from adjuvant chemotherapy:
        • Particularly those older than 50 years
• Study design:
  • The trial enrolled:
    • 9,719 women with HR-positive, HER2-negative, node-negative breast cancer
  • Patients with a recurrence score (RS) 0 to 10 received endocrine therapy alone; those with RS 26 to 100 received chemoendocrine therapy; and those with RS 11 to 25 were randomized to endocrine therapy alone versus chemoendocrine therapy
• Primary result:
  • Among women with RS 11 to 25:
    • Endocrine therapy alone was noninferior to chemoendocrine therapy for invasive disease–free survival:
    • At 9 years:
      • Invasive disease–free survival was 83.3% with endocrine therapy alone versus 84.3% with chemoendocrine therapy
    • Distant recurrence rates were also very similar:
      • This established that for the overall randomized group:
        • Adding chemotherapy did not provide a clinically meaningful benefit
  • Age-specific nuance:
    • The critical nuance from TAILORx is age
    • In women 50 years or younger:
      • There appeared to be some chemotherapy benefit in subsets with RS 16 to 25:
        • Especially at the upper end of that range
    • By contrast, women older than 50 with RS 11 to 25 generally did not benefit from chemotherapy
    • The NCI summary estimated that chemotherapy can be safely avoided in about 70% of women with this common breast cancer subtype, including:
      • Any age with RS 0 to 10
      • Age > 50 with RS 11 to 25
      • Age ≤ 50 with RS 11 to 15
• Low-score group (RS 0 to 10):
  • The earlier prospective TAILORx report showed that women with RS 0 to 10 treated with endocrine therapy alone had very low recurrence rates:
    • Supporting omission of chemotherapy in this low-risk group
  • High-score group (RS 26 to 100):
    • Patients with RS 26 to 100 were assigned to chemotherapy plus endocrine therapy
    • Follow-up analyses supported the standard recommendation to offer chemotherapy to this high-risk group:
      • NCI reported that women in this category had strong 5-year outcomes with chemoendocrine therapy:
        • Reinforcing that these patients should still be considered for systemic intensification rather than endocrine therapy alone
• Clinical risk analysis:
  • A secondary analysis integrating clinical risk (tumor size and grade) found that clinical risk adds prognostic information:
    • But was not clearly predictive of chemotherapy benefit in the overall population:
      • However, in women 50 years or younger, chemotherapy benefit was more apparent in those with RS 16 to 20 and high clinical risk, and in those with RS 21 to 25 regardless of clinical risk
• Practical takeaways for the surgical oncologist:
• TAILORx matters because it reframes postoperative discussions after definitive surgery in node-negative HR+ / HER2- disease:
  • Genomic testing is central to adjuvant planning after surgery in appropriate patients
  • TAILORx made the recurrence score part of standard decision-making:
    • Not just a prognostic adjunct
  • Chemotherapy can often be omitted in postmenopausal or older patients with RS 11 to 25:
    • Which is highly relevant when counseling patients after lumpectomy or mastectomy
  • In premenopausal or younger patients, especially ≤v50 years with RS 16 to 25:
    • The conversation is more nuanced:
      • These patients may derive benefit from chemotherapy:
        • Though some experts note that part of this benefit may reflect ovarian function suppression rather than direct cytotoxic effect alone
• TAILORx applies to node-negative disease
  • For 1 to 3 positive nodes:
    • The more relevant prospective trial is RxPONDER, not TAILORx
• Bottom line:
  • TAILORx changed practice by showing that adjuvant chemotherapy is unnecessary for most women with node-negative HR-positive / HER2-negative early breast cancer who have a midrange Oncotype DX recurrence score, particularly those older than 50
  • The major exception is the younger / premenopausal subgroup with RS 16 to 25:
    • Where chemotherapy may still offer benefit and multidisciplinary discussion remains essential
• Key references:
  • Sparano JA, Gray RJ, Makower DF, et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. N Engl J Med. 2018;379:111-121. 
  • Sparano JA, Gray RJ, Ravdin PM, et al. Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer. N Engl J Med. 2019;380:2395-2405. 
  • National Cancer Institute. TAILORx trial finds most women with early breast cancer do not benefit from chemotherapy. 2018. 
    National Cancer Institute PDQ. Breast Cancer Treatment (PDQ®), updated 2025. 

– Borderline resectable oral cavity cancer is a surgical dilemma
Can chemo-immunotherapy increase operability?

A new Phase II trial suggests yes

🧪 NeoLOCUS trial (Lancet Regional Health SE Asia)

Regimen:
Carboplatin + nab-paclitaxel + low-dose nivolumab
•oral metronomic therapy (methotrexate + celecoxib + erlotinib)

🎯 Population
Borderline resectable OSCC
n = 34

📊 Key results

• ORR: 66.6%
• R0 resection after 2 cycles: 75.7%
• Overall surgical conversion: 90.3%
• Major pathological response: 41%
• pCR: 13.8%

🧬 Interesting biology
Good responders showed reduction in FOXP3+ Tregs, suggesting immune-microenvironment modulation.

⚠️ Safety
Grade ≥3 toxicity: 14.7%
No treatment-related deaths.

💡 Why this matters

Borderline OSCC often fails surgery after standard NACT.
This low-dose IO + metronomic + chemo strategy may offer an affordable outpatient approach in LMIC settings.

But this is single-arm Phase II → randomized validation needed.

Abstract

Context: Patients with elevated parathyroid hormone (PTH) and consistently normal serum calcium levels, in whom secondary causes of hyperparathyroidism have been excluded, may represent the earliest presentation of primary hyperparathyroidism (PHPT).

Objective: The objective of the study was to characterize patients with normocalcemic PHPT referred to a bone disease unit.

Design: This was a longitudinal cohort study.

Setting: Ambulatory patients were referred to the metabolic bone disease unit.

Patients: The study population included 37 patients [aged 58 yr, range 32–78; 95% female; serum calcium, 9.4 ± 0.1 (SEM) mg/dl (2.3 ± 0.02 mmol/liter), reference range, 8.5–10.4 (2.1–2.6 mmol/liter); PTH, 93 ± 5 pg/ml].

Interventions: Interventions included yearly (median 3 yr; range 1–8 yr) physical examination, biochemical indices, and bone mineral density (BMD).

Main Outcome Measures: We measured the development of features of PHPT.

Results: Evaluation for classical features of PHPT revealed a history of kidney stones in five (14%), fragility fractures in four (11%), and osteoporosis in 57% [spine (34%), hip (38%), and/or distal one third radius (28%)]. BMD did not show preferential bone loss at the distal one third radius (T scores: spine, −2.00 ± 0.25; hip, −1.84 ± 0.18; one third radius, −1.74 ± 0.22). Further signs of PHPT developed in 40% (seven hypercalcemia; one kidney stone; one fracture; two marked hypercalciuria; six had >10% BMD loss at one or more site(s) including four patients developing World Health Organization criteria for osteoporosis). Seven patients (three hypercalcemic, four persistently normocalcemic) underwent successful parathyroidectomy.

Conclusions: Patients seen in a referral center with normocalcemic hyperparathyroidism have more substantial skeletal involvement than is typical in PHPT and develop more features and complications over time. These patients may represent the earliest form of symptomatic, rather than asymptomatic, PHPT.

Lowe, Hyesoo et al. “Normocalcemic primary hyperparathyroidism: further characterization of a new clinical phenotype.” The Journal of clinical endocrinology and metabolism 92 8 (2007): 3001-5 .

#Arrangoiz #ParathyroidSurgeon #ParathyroidExpert #Hyperparathyroidism #PrimaryHyperparathyroidism #CancerSurgeon #EndocrineSurgery #Teacher #Surgeon #HeadandNeckSurgeon #SurgicalOncologist #ParathyroidAdenoma #Hypercalcemia #ElevatedCalciumLevels #Miami #MountSinaiMedicalCenter #MSMC #Mexico #Hialeah

• Type A:
  • Adherent to the posterior thyroid parenchyma:
    • Posterior to the upper pole of the thyroid:
      • But not intrathyroidal
  • Type A glands are in the accepted, expected location of a normal parathyroid gland
• Type B:
  • Behind the thyroid parenchyma
  • Type B glands are exophytic to the thyroid parenchyma and lie in the tracheoesophageal groove:
    • This category includes adenomas in:
      • Retroesophageal, retropharyngeal, high lateral pharyngeal, and carotid sheath locations
  • A ‘‘B+’’ subcategory can be used to document the location of adenomas above the level of the hyoid bone:
    • The ‘‘+’’ is meant to reflect cranial elevation
• Type C:
  • Caudal to the thyroid parenchyma:
    • In the tracheoesophageal groove
  • A type C gland is more inferior than a type B gland on lateral images:
    • Located inferior to the inferior pole of the thyroid (closer to the clavicle)
• Type D:
  • Directly over the recurrent laryngeal nerve:
    • At the level of the inferior thyroid vessels
  • The dissection may be difficult:
    • Because a type D gland is dangerously close to the recurrent laryngeal nerve
• Type E:
  • Located in the external aspect of the inferior pole of the thyroid
  • A type E gland is in a location that is:
    • More superficial in an anterior–posterior plane than the recurrent laryngeal nerve:
      • It is the easiest to resect
• Type F:
  • ‘‘Fallen’’ into the thyrothymic ligament:
    • Below the inferior pole of the thyroid in a pretracheal plane
  • A type F gland is frequently referred to as an ectopic gland:
    • Its resection usually involves:
      • Transcervical delivery of the thyrothymic ligament or superior portion of the thymus
• Type G:
  • A gauge, true intrathyroidal gland location

• This nomenclature system has been designed that takes into account the pathologic position of the parathyroid glands (Figure):
  • Superior and inferior glands:
    • Are defined by the location of the gland’s pedicle and its relationship to the RLN:
      • Superior parathyroid glands:
        • Anatomically have a vascular pedicle superior and lateral to the RLN (type A through D glands)
      • Inferior parathyroid glands:
        • Anatomically have a vascular pedicle inferior and medial to the RLN (type D through F glands)
    • Type G glands:
      • Represent intrathyroidal parathyroid lesions
  • This information not only helps radiologists communicate potential parathyroid lesions of interest to surgeons:
    • But also helps surgeons direct their dissection in relation to the RLN

• Differential Diagnosis of Hypercalcemia:
  • Primary hyperparathyroidism:
    • Solitary adenoma:
      • 85% to 90% of the cases
    • Multigland Disease:
      • Multigland hyperplasia:
        • 3% of the cases
      • Doble adenoma:
        • 6% to 9% of the cases
      • Triple adenoma:
        • 0.3% of the cases
  • Secondary hyperparathyroidism
  • Tertiary hyperparathyroidism
  • Familial hypocalciuric hypercalcemia
  • Medications:
    • Lithium
    • Hydrochlorothiazide
  • Malignancy:
    • Parathyroid carcinoma
    • Multiple myeloma
    • Tumors producing PTH-related peptide:
      • Ovarian cancer
      • Lung cancer
    • Acute or chronic leukemia
  • Granulomatous diseases:
    • Sarcoidosis, histioplasmosis, tuberculosis
  • Thyrotoxicosis
  • Paget disease
  • Increased intake:
    • Milk-alkali syndrome
    • Vitamin A toxicity
    • Vitamin D toxicity

• Primary hyperparathyroidism (PHPT):
  • Is caused by an inappropriate, autonomous  secretion of parathyroid hormone (PTH) by the parathyroid gland(s):
    • Which leads to an elevated serum calcium concentration or wide variations of the serum calcium concentration
  • Single gland disease:
    • Caused by a single, enlarged, overactive gland, is found in 85% to 90% of cases
  • Multiple gland disease occurs in 10% to 15% of the cases:
    • Multiple gland disease may consist of:
      • Double adenomas (6% to 9% of the cases)
      • Four-gland hyperplasia (3% of the cases)
      • Three enlarged and one normal appearing gland (0.3% of the cases).
        • Because asymmetric hyperplasia is common, it is difficult to distinguish between multiple adenomas and hyperplasia and the term multiple gland disease is preferred
  • PHPT in the United States usually presents quite early:
    • Often when hypercalcemia is noted during routine laboratory testing
  • Signs may include:
    • Nephrolithiasis, decreased bone density, and fragility fractures, and subjective symptoms may include fatigue, cognitive changes, depression, constipation and other gastrointestinal complaints, musculoskeletal pain, nocturia, and rarely pruritus:
      • Many patients may appear asymptomatic:
        • A detailed history often uncovers symptoms:
          • 95% of the cases have symptoms when appropriate history is taken:
            • The recently revised guidelines for asymptomatic PHPT include a more extensive evaluation of the skeletal and renal systems
  • A family history of endocrine disorders should be investigated:
    • As hyperparathyroidism alone can be familial or can present as a component of multiple endocrine neoplasia (MEN) types 1 and 2A

👉Hyperparathyroidism is associated with a wide array of symptoms related to neurocognitive and psychiatric function

👉Patients often report difficulties with memory and concentration, “brain fog”, mood related problems including depression, anxiety and irritability

👉They may also report weakness, general fatigue, sleep disturbance, joint and muscle pain

👉While the specific etiology of these symptoms is not clearly defined, they have been noted with increased frequency in this population

👉Read more at:

👉https://www.jscimedcentral.com/jounal-article-pdf/JSM-Head-and-Neck-Cancer-Cases-and-Reviews/headneck-1-1002.pdf

• Intraoperative rapid PTH does not itself define cure:
  • It is an intraoperative predictor of adequacy of resection
• Formal cure after parathyroidectomy:
  • Is still biochemical eucalcemia lasting at least 6 months
• Rapid PTH works:
  • Because intact PTH has a short half-life:
    • Roughly 3 to 5 minutes:
      • So levels should fall quickly after all hyperfunctioning tissue is removed
• The AAES guidelines:
  • Recommend intraoperative PTH monitoring with a reliable protocol for minimally invasive parathyroidectomy:
    • They note cure rates of about 97% to 99% in selected patients when adjunctive IPM is used
• Core concept:
  • The practical question in the OR is:
    • “Has all hypersecreting parathyroid tissue been removed?”
      • Rapid PTH helps answer that in real time
• Most protocols use a baseline sample before incision and / or immediately before excision:
  • Then a post-excision level at 10 minutes, with an additional 20-minute sample when the decline is borderline or delayed
• The most common reason the curve is misleading:
  • Is a PTH spike from gland manipulation:
    • Which is why many surgeons rely on the highest pre-incision or pre-excision value rather than only the pre-incision sample 
• Main intraoperative PTH protocols
  • The classic comparative study of 260 patients with concordant imaging:
    • Found overall accuracy of:
      • 97.3% for Miami, 92.3% for Vienna, 83.8% for Rome, and 65% for Halle criteria
    • In that same study:
      • Miami criteria was the best-balanced criterion for predicting cure:
        • Whereas Rome and Halle were somewhat better for detecting multigland disease but at the cost of more negative conversions to bilateral exploration
• The Miami criterion:
  • Is the most widely used:
    • A > 50% fall from the highest pre-incision or pre-excision PTH level, measured 10 minutes after excision of the abnormal gland
  • In the major Miami experience and subsequent reviews:
    • This approach achieved about 97% to 98% sensitivity, 97% specificity, ~99% PPV, and ~97% to 98% overall accuracy for postoperative eucalcemia
  • Long-term follow-up from the Miami group also showed durable outcomes with very low recurrence after focused surgery guided by intraoperative rapid PTH
  • This is why, in everyday endocrine surgery practice, the Miami criterion is usually the most useful protocol:
    • It is easy to remember, fast, reproducible, and has the best overall balance between avoiding persistent disease and avoiding unnecessary wider exploration
  • A 2024 network meta-analysis including 72 studies and 19,072 patients found that among conventional criteria:
    • The Miami criterion had the best diagnostic properties overall
• Vienna criterion:
  • The Vienna criterion also uses a > 50% drop at 10 minutes:
    • But the reference is the defined pre-incision baseline rather than the highest pre-excision value
  • It was designed to standardize interpretation and improve identification of multigland disease
  • In the comparative dataset above:
    • Vienna performed well, with 92.3% overall accuracy:
      • But still not as well as Miami for routine prediction of cure
    • In practical terms, Vienna is reasonable if your team insists on a strict, fixed baseline, but it is less forgiving when pre-excision manipulation creates a spike:
      • That is one reason many high-volume groups prefer Miami’s use of the highest available baseline
• Halle criterion:
  • Is much stricter:
    • Success is called only when PTH drops into the low-normal range:
      • Classically around 35 pg/mL:
        • Shortly after excision
  • This gives excellent specificity, but it performs poorly as a routine stopping rule because many successfully treated patients still have PTH levels above that threshold intraoperatively:
    • Especially if starting levels are high or clearance is delayed
  • In the Barczyński comparison, Halle had 100% specificity but only 65% overall accuracy:
    • Meaning it would trigger many unnecessary further explorations
  • For that reason, Halle is usually not the best default criterion for standard sporadic PHPT with concordant imaging:
    • It is too strict for routine use
• Rome criterion:
  • Is a more complex, stricter protocol
  • In one description, it requires a > 50% fall from the highest pre-excision level and / or a value within the normal range and / or an additional fall by 20 minutes
  • The point of Rome is to improve detection of persistence and multigland disease:
    • Especially when the early curve is ambiguous
  • A 2022 study evaluating the Rome approach found that the 20-minute / baseline ratio:
    • Had the highest diagnostic significance and suggested the 20-minute sample is particularly informative
  • Rome can be useful when the 10-minute value is borderline, when preoperative localization is less reliable, or when multigland disease is a real concern:
    • But as a standard protocol for all focused cases, it adds complexity and tends to increase exploration without clearly outperforming Miami for overall cure prediction
• What do meta-analyses say about using ioPTH at all?
  • Beyond comparing criteria, the broader question is whether using ioPTH improves outcomes
  • A 2021 systematic review / meta-analysis of 28 studies and 13,323 patients found operative failure rates of 3.2% with ioPTH versus 5.8% without ioPTH:
    • With a significant reduction in persistent / recurrent PHPT when ioPTH was used
  • Another 2021 systematic review / meta-analysis focused on minimally invasive parathyroidectomy included 12 studies and 2,290 patients and found that ioPTH use was associated with higher cure rates (OR 3.88, 95% CI 2.12–7.10) and a lower need for reoperation:
    • It did increase conversion to bilateral exploration, but without higher morbidity
  • So the evidence supports the value of ioPTH, especially when doing focused or minimally invasive surgery and when multigland disease is a concern
• Are stricter cutoffs better?
  • Usually, not enough to justify routine adoption
  • Newer work continues to test stricter thresholds:
    • A 2025 ROC analysis found that a 60% drop gave the best balance of sensitivity and specificity in that cohort, outperforming 50% and 70% on AUC, but the authors also cautioned that stricter thresholds may cause overtreatment and unnecessary exploration
    • Similarly, a 2025 two-center study suggested that combining the Miami rule with normalization to the reference range may help in selected cases, but the overall literature still favors the Miami criterion as the best general-purpose rule, which is consistent with the large network meta-analysis
• Practical interpretation in the OR
  • A resident-friendly approach is:
    • Draw pre-incision and pre-excision PTH
    • Remove the suspected gland
    • Check 10-minute PTH
    • If > 50% drop from the highest baseline → likely cure, stop if anatomy and clinical context fit
    • If borderline or not adequate → wait for 20-minute level and continue exploration if still not satisfactory
    • That approach handles the common real-life issues:
      • Manipulation spikes, delayed clearance, and occult multigland disease
• When rapid PTH is especially helpful:
  • Rapid PTH is most helpful in:
    • Focused / minimally invasive parathyroidectomy
    • Discordant or equivocal localization
    • Suspicion for multigland disease
    • Reoperative surgery
    • Cases where confirmation of adequacy of excision will determine whether you stop or proceed to wider exploration
• Bottom line: which protocol is most useful?
  • For most sporadic PHPT cases, especially with focused surgery:
    • The Miami criterion is the most useful protocol:
      • It has the best combination of simplicity, speed, evidence base, and diagnostic performance, and it remains the most widely adopted and best-supported criterion in comparative studies and network meta-analysis
• Key references:
  • Wilhelm SM, et al. AAES Guidelines for Definitive Management of Primary Hyperparathyroidism. JAMA Surg. 2016. 
  • Barczyński M, et al. Evaluation of Halle, Miami, Rome, and Vienna intraoperative iPTH assay criteria. Langenbecks Arch Surg. 2009. 
  • Khan ZF, et al. Intraoperative Parathyroid Hormone Monitoring in the Surgical Management of Sporadic PHPT. Endocrinol Metab. 2019. 
  • Quinn AJ, et al. Systematic review/meta-analysis of ioPTH in MIP. JAMA Otolaryngol Head Neck Surg. 2021. 
  • Medas F, et al. Systematic review/meta-analysis of rapid ioPTH. Int J Surg. 2021. 
  • Staibano P, et al. Network meta-analysis of diagnostic test accuracy. JAMA Otolaryngol Head Neck Surg. 2024/2025 indexing. 

• Prevalence of PHPT during pregnancy:
  • Is reported to be between 0.15% and 1.4%
• PHPT during pregnancy may have serious consequences to the mother and to the fetus:
  • If it remains unrecognized or untreated:
    • In up to 80% of patients, it is not recognized due to physiological changes during pregnancy that mask gestational PHPT, such as:
      • Hemodilution:
        • Related to intravascular fluid expansion
      • Hypoalbuminemia
      • Increased glomerular filtration rate:
        • Resulting in hypercalciuria
      • Transplacental transfer of calcium
  • Clinical presentation of PHPT durign pregnagncy may range from:
    • Hyperemesis, lethargy, hypertension, thirst, abdominal pain, depression, constipation, bone fracture, maternal heart rhythm disorders, maternal hypertension to preeclampsia, nephrolithiasis, pancreatitis, hyperemesis gravidarum, and hypercalcemic crisis:
      • Because the understanding of this concept and standard monitoring of all pregnant patients in developed countries:
        • The presentation of PHPT during pregnancy is very mild:
          • It is diagnosed in earlier stages
  • Sestamibi scan is contraindicated during pregnancy:
    • Due to radiation exposure risk to the fetus:
      • Ultrasound is the only diagnostic option since it carries no risk of radiation exposure and is easy to perform
  • Management of PHPT during pregnancy:
    • Should be individualized based on symptoms and severity of hypercalcemia:
      • Parathyroidectomy is indicated in symptomatic patients and patients with severe hypercalcemia:
        • When calcium level is elevated above 11 mg/dL (2.74 mmol/L)
      • Parathyroidectomy should be performed only in the second trimester:
        • To prevent miscarriage and anesthetic drugs exposure in the first trimester or spontaneous delivery in the third trimester
      • Mild form of PHPT causes low risk of maternal and obstetrical complications:
        • Therefore the patients can be managed conservatively, and parathyroidectomy can be deferred until after the delivery
      • Some medications, such as bisphosphonates, are contraindicated during pregnancy
      • Calcitonin:
        • Showed limited data and poor effectiveness:
          • But it does not cross the placenta and appears to be safe
      • Cinacalcet:
        • Has shown good results in several studies:
          • Although safety data are limited
      • Recent paper published by Rigg et al. retrospectively reviewed data of 28 pregnant patients with PHPT (22 managed medically and 6 surgically by elective parathyroidectomies):
        • Showed that 30% of those who were managed medically developed preeclampsia, and 66% managed medically had preterm deliveries